Journal article

Association of Somatic Driver Alterations With Prognosis in Postmenopausal, Hormone Receptor-Positive, HER2-Negative Early Breast Cancer A Secondary Analysis of the BIG 1-98 Randomized Clinical Trial

Stephen J Luen, Rebecca Asher, Chee Khoon Lee, Peter Savas, Roswitha Kammler, Patrizia Dell'Orto, Olivia Maria Biasi, David Demanse, Lellean JeBailey, Sinead Dolan, Wolfgang Hackl, Beat Thuerlimann, Giuseppe Viale, Marco Colleoni, Meredith M Regan, Sherene Loi



Importance: A range of somatic driver alterations has been described in estrogen receptor-positive, HER2-negative (ER+/HER2-) early breast cancer (BC); however, the clinical relevance is unknown. Objective: To investigate associations of driver alterations with prognosis and the role of PIK3CA mutations in prediction of benefit associated with endocrine therapy in postmenopausal patients with ER+/HER2- early BC treated with tamoxifen or letrozole. Design, Setting, and Participants: The Breast International Group (BIG) 1-98 trial randomized 8010 postmenopausal patients with hormone receptor-positive, operable, invasive BC to monotherapy with letrozole, tamoxifen, or a sequential strategy for ..

View full abstract


Awarded by Susan G. Komen for the Cure

Funding Acknowledgements

This translational research was funded in part by Novartis (partial funding of tissue block collection and full funding of next-generation sequencing at Foundation Medicine) and Susan G. Komen for the Cure Promise Grant (nucleic acid extraction, grant KG080081 to Drs Viale and Regan). The Breast International Group (BIG) 1-98 trial was supported by Novartis. The International Breast Cancer Study Group (IBCSG), which coordinated the BIG 1-98 trial, was also supported by The Swedish Cancer Society, The Swedish Research Council, The Cancer Council Australia, Australia and New Zealand Breast Cancer Trials Group, Frontier Science and Technology Research Foundation, Swiss Group for Clinical Cancer Research, Cancer Research Switzerland/Oncosuisse, and the Foundation for Clinical Cancer Research of Eastern Switzerland. Dr Luen is supported by the University of Melbourne. Prof Loi is supported by Breast Cancer Research Foundation of Australia and the John Colebatch Cancer Council Victoria Clinical fellowship.